3-183829177-C-T

Variant names:

• chr3-183829177-C-T
• rs263003
• ENST00000639401.1:c.1028+4315G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000639401.1(ENSG00000283765):​c.1028+4315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 240,300 control chromosomes in the GnomAD database, including 61,412 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37448 hom., cov: 31)
  • Exomes 𝑓: 0.73 (23964 hom.)
• Consequence: ENSG00000283765 ENST00000639401.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

Genes affected

ENSG00000283765 (HGNC:):

PARL (HGNC:18253): (presenilin associated rhomboid like) This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7	c.*421G>A		downstream_gene_variant		ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283765	ENST00000639401.1	c.1028+4315G>A		intron_variant	Intron 9 of 10	5		ENSP00000491227.1
PARL	ENST00000317096.9	c.*421G>A		downstream_gene_variant		1	NM_018622.7	ENSP00000325421.5

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105856 AN: 151870 Hom.: 37416 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.729 AC: 64357 AN: 88312 Hom.: 23964 AF XY: 0.729 AC XY: 33553 AN XY: 46014

Gnomad4 AFR exome AF: 0.617

Gnomad4 AMR exome AF: 0.807

Gnomad4 ASJ exome AF: 0.814

Gnomad4 EAS exome AF: 0.962

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.633

Gnomad4 NFE exome AF: 0.712

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.697 AC: 105934 AN: 151988 Hom.: 37448 Cov.: 31 AF XY: 0.691 AC XY: 51369 AN XY: 74292

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.731

Alfa AF: 0.727 Hom.: 38984

Bravo AF: 0.710

Asia WGS AF: 0.839 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs263003; hg19: chr3-183546965;